e15620 Background: Patients with metastatic colorectal cancer (mCRC) and severe hepatic dysfunction from liver metastases are routinely excluded from trials, leaving limited evidence to guide chemotherapy dosing, safety, and expected benefit. Methods: MEDLINE and Embase were searched from inception to January 15, 2026. We included English-language reports of adults with mCRC and liver dysfunction attributed to hepatic metastases who received cytotoxic chemotherapy (fluoropyrimidine-, oxaliplatin-, and/or irinotecan-based regimens; biologics allowed). Data were extracted in by two independent reviewers. Outcomes included grade ≥3 toxicity, treatment-related mortality, bilirubin response, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Where reported, individual patient data (IPD) were pooled for descriptive analyses and Kaplan–Meier estimation. Results: Of 6775 records screened, fourteen reports were included and provided extractable IPD for 33 patients. Median baseline bilirubin was 7.4 mg/dL (range 1.9–28.1). Most patients received oxaliplatin-based therapy (25/33, 76%); upfront dose reductions were common (25/28, 89%), with subsequent dose escalation in 19/25 (76%) when reported. A ≥50% bilirubin reduction occurred in 25/32 (78%), and bilirubin normalized ( < 1.3 mg/dL) in 18/32 (56%); median time to normalization was 56 days (IQR 39–67; n = 11). Among patients with safety reporting, grade ≥3 adverse events occurred in 9/21 (43%) and treatment-related mortality in 1/22 (4.5%). ORR was 10/20 (50%) among patients with response assessment. In available IPD, Kaplan–Meier median PFS was 7.3 months (n = 22) and median OS 8.2 months (n = 30). Conclusions: In the sparse evidence available for this high-risk population, chemotherapy—most often initiated at reduced dose and escalated as liver function improved—was frequently associated with biochemical improvement and occasional objective responses, with uncommon reported treatment-related mortality. Given substantial reporting limitations and small study sizes, there is potential for reporting bias, and prospective data are needed. Nonetheless, these findings suggest that severe hyperbilirubinemia due to tumor burden should not automatically preclude cautious, individualized initiation of systemic chemotherapy with close monitoring in selected patients.
Bailey et al. (Thu,) studied this question.